Regulation of dopaminergic markers expression in response to acute and chronic morphine and to morphine withdrawal

Abstract Dopamine ( DA ) is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. Dysfunction of DA homeostasis leading to high or low DA levels is causally linked to addiction. Previously, it has been proposed that the transcription factors Nurr 1 and Pitx 3, which are critical for transcription of a set of genes involved in DA metabolism in the mesolimbic pathway, are associated with addiction pathology. Using quantitative real‐time polymerase chain reaction, immunofluorescence and W estern blotting, we studied the effects of single morphine administration, morphine dependence and withdrawal on the DA markers DA transporters ( DAT ), vesicular monoamine transporters ( VMAT 2) and DA 2 receptor subtype ( DRD 2), DA 1 receptor subtype as well as tyrosine hydroxylase ( TH ) in the ventral tegmental area ( VTA ) and/or nucleus accumbens ( NAc ). In addition, Nurr 1 and Pitx 3 expression was also measured. Present data showed a high degree of colocalization of Nurr 1 and Pitx 3 with TH + neurons in the VTA . We found that the increased Nurr 1 and/or Pitx 3 levels during morphine dependence and in morphine‐withdrawn rats were associated to an increase of DAT , VMAT 2 and DRD 2. Altogether, present data indicate that morphine dependence and withdrawal induced consistent alterations of most of the DA markers, which was correlated with transcription factors involved in the maintenance of DA neurons in drug‐reward pathways, suggesting that Nurr 1 and Pitx 3 regulation might be associated with controlling adaptation to chronic morphine and to morphine withdrawal‐induced alterations of DA neurons activity in the mesolimbic pathway.